Matsui S, Jones G L, Woolley M J, Lane C G, Gontovnick L S, O'Byrne P M
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Am Rev Respir Dis. 1991 Dec;144(6):1287-90. doi: 10.1164/ajrccm/144.6.1287.
The role of oxygen radicals in causing ozone-induced airway hyperresponsiveness in dogs was examined by pretreating dogs with allopurinol and/or deferoxamine mesylate (desferal), which are inhibitors of oxygen radical generation, before ozone inhalation. Acetylcholine airway responsiveness was measured before and after either air or ozone inhalation (3 ppm for 20 min) on 5 experimental days separated by at least 2 wk. On each day, the dogs were pretreated intravenously with allopurinol (50 mg/kg) followed by inhaled desferal (1,000 mg inhalation) or with allopurinol followed by the diluent for desferal or with the diluent for allopurinol and desferal or with both diluents. The effect of ozone on acetylcholine airway responsiveness was expressed as the differences in the log-transformed preozone-postozone acetylcholine provocative concentrations. When dogs received both diluents or either treatment alone, ozone inhalation caused airway hyperresponsiveness. The mean log differences for the preozone-postozone acetylcholine provocative concentration were 0.804 (SEM, 0.17) for both diluents, 0.524 (SEM, 0.16) for allopurinol alone, and 0.407 (SEM, 0.22) for desferal alone. However, the combination of allopurinol and desferal significantly inhibited the development of ozone-induced airway hyperresponsiveness, the log difference being 0.195 (SEM, 0.11) (p less than 0.05), without inhibiting ozone-induced neutrophil influx into the airways. The results suggest that the production of oxygen radicals is important in the pathogenesis of ozone-induced airway hyperresponsiveness.
通过在犬吸入臭氧之前用别嘌呤醇和/或甲磺酸去铁胺（去铁敏）对犬进行预处理，研究了氧自由基在犬臭氧诱导的气道高反应性中的作用，别嘌呤醇和甲磺酸去铁胺是氧自由基生成的抑制剂。在至少间隔2周的5个实验日中，测量吸入空气或臭氧（3 ppm，持续20分钟）前后的乙酰胆碱气道反应性。每天，犬静脉注射别嘌呤醇（50 mg/kg），随后吸入去铁敏（1000 mg吸入剂），或先注射别嘌呤醇，再注射去铁敏稀释剂，或注射别嘌呤醇和去铁敏的稀释剂，或注射两种稀释剂。臭氧对乙酰胆碱气道反应性的影响以对数转换后的臭氧吸入前-吸入后乙酰胆碱激发浓度的差异表示。当犬接受两种稀释剂或单独任何一种处理时，吸入臭氧会导致气道高反应性。两种稀释剂组臭氧吸入前-吸入后乙酰胆碱激发浓度的平均对数差异为0.804（标准误，0.17），单独使用别嘌呤醇组为0.524（标准误，0.16），单独使用去铁敏组为0.407（标准误，0.22）。然而，别嘌呤醇和去铁敏的联合使用显著抑制了臭氧诱导的气道高反应性的发展，对数差异为0.195（标准误，0.11）（p<0.05），且不抑制臭氧诱导的中性粒细胞流入气道。结果表明，氧自由基的产生在臭氧诱导的气道高反应性的发病机制中起重要作用。
